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Plant Profiler

Garlic (Allium sativum)


<em>Allium sativum</em> Image
Synonyms / Common Names / Related Terms
2-propenesulfenic acid, aged garlic extract, aglio, ail, ail commun, ajo, ajoene, akashneem, alisat, allicin, Allii sativi bulbus, alliinase, allium, allyl mercaptan, alubosa elewe, Amaryllidaceae (family), ayo-ishi, ayu, banlasun, camphor of the poor, clove garlic, da-suan, dai toan, dasuan, dawang, diallyl disulphide, diallyl sulfide, diallyl sulphide, dipropyl disulphide, dipropyl sulphide, dra thiam, foom, garlic clove, garlic corns, garlic extract, garlic oil, Gartenlauch, hom khaao, hom kia, hom thiam, hua thiam, kesumphin, kitunguu-sumu, knoblauch, kra thiam, Krathiam, krathiam cheen, krathiam khaao, Kwai®, Kyolic, l'ail, lahsun, lai, la-juan, lasan, lashun, la-suan, lasun, lasuna, lauch, lay, layi, lehsun, lesun, Liliaceae (family), lobha, majo, naharu, nectar of the gods, Ninniku, pa-se-waa, poor man's treacle, rason, rasonam, rasun, rust treacle, rustic treacles, S-allylcysteine (SAC), seer, skordo, sluon, stinking rose, sudulunu, tafanuwa, ta-suam, ta-suan, tellagada, Tellagaddalu, thiam, Thioallyl derivative, Thiosulfinates, toi thum, tum, umbi bawang putih, vallaippundu, Velluli, vellulli, verum, Vinyl dithiin.


Mechanism of Action

Pharmacology:

  • Constituents: Chemical analysis in the 1800s attributed garlic's activity to the sulfur containing garlic oil. In the mid 1900s an American chemist named the strong smelling liquid "allicin".18 The sulfur compound alliin (S-allyl-l-cysteine sulfoxide) produces allicin (diallyl thiosulfinate) via the enzyme allinase when the bulb is crushed or ground. Other sulfur compounds, peptides, steroids, terpenoids, flavonoids, and phenols have increasingly been identified as possible active ingredients19,20,10 as allicin is metabolized. The exact mechanism of action underlying garlic's effects remains unknown and may vary according to the preparation21 and the therapeutic effect.
  • Garlic appears to exert numerous effects on the cardiovascular system, and Atherosclerosis in particular, beyond the reduction of serum lipids. There are possibly multiple protective effects of garlic22,12,23, including inhibition of platelet aggregation and enhancement of fibrinolysis. Wild garlic (Allium ursinum) has been reported to contain similar amounts of sulfur-containing compounds (thiosulfinates and ajoenes) as garlic (Allium sativum), and to exert similar effects on cyclooxygenase, 5-lipoxygenase, angiotensin converting enzyme, and platelet aggregation.24
  • Lipid-lowering Effects: Garlic's lipid lowering effects may occur via inhibition of HMG-CoA reductase or other enzymes25,26,27,28,29,30,31,32, possibly by diallyl di- and trisulphide components of garlic.33,34 Other suggested mechanisms include increased loss of bile salts in feces and mobilization of tissue lipids into circulation35, as garlic has a profound effect on post-prandial hyperlipidemia.36 Wild garlic (Allium ursinum) has shown similar efficacy to garlic (Allium sativum) in decreasing hepatocyte cholesterol synthesis In vitro.24,37 Aged garlic extract and its constituents have been shown to inhibit Cu2+-induced oxidative modification of low-density lipoprotein.38 Aged garlic extract and its constituent S-allylcysteine have been found to protect vascular endothelial cells from injury caused by oxidized LDL.39
  • Animal and human cell lines have demonstrated reductions in vascular tissue lipids40,41, fatty streak formation and atherosclerotic plaque size.22,42,43,44,12,40,45 The mechanism of action may include reduction of lipoprotein oxidation, as demonstrated In vitro38,39,46 and in vivo47, possibly due to organosulfur compounds in garlic.48 However, this hypothesis has been in dispute based on a six-month trial in moderately hypercholesterolemic volunteers which failed to demonstrate any effects of garlic supplementation on lipoprotein oxidation.49
  • Platelet Effects: Garlic and its derived compound ajoene have demonstrated inhibition of platelet aggregation In vitro and in animals50,51,52,15,9,53,54,55,56,57,58,59, and reduction of platelet-dependent thrombus formation.60,61 Research has demonstrated inhibition of platelet aggregation in hypercholesterolemic men62, in healthy subjects, in patients with coronary artery disease63,64,65,66,67, and in subjects with cerebrovascular risk factors3,11. However, a study using a low dietary dosage found no such effects.68 Raw garlic has been shown to inhibit platelet cyclooxygenase In vitro.50 Dose-dependent inhibition of cyclooxygenase in human placenta villi was observed with garlic and with allicin-negative (acid washed) garlic.69 Anti-platelet activity may be attributable to garlic constituents including adenosine, allicin and paraffinic polysulfides.70 Compared to raw garlic, a boiled aqueous garlic extract demonstrated an approximately 50% decrease in platelet aggregation at identical concentrations50, 59, suggesting that cooking garlic may reduce anti-platelet effects. Raw garlic has been shown to reduce serum thromboxane B2 in animal and human research63, 35, at a dose of one clove per day71. However, boiling garlic prior to administration appears to reduce or abolish this effect64, again suggesting a negative impact of cooking on garlic's anti-platelet activity.
  • Fibrinolytic Effects: Increased fibrinolytic activity may account for some degree of garlic's anti-clotting effects72, 20, 73, involving fibrinogen and plasminogen16. Both raw garlic and fried garlic have demonstrated significant increases in fibrinolytic activity in man74, as well as essential oil from raw garlic36. An increase in fibrinolytic activity in patients with ischemic heart disease was found to be maintained after 7-8 weeks of continued therapy.75, 76 However, one study reported that fibrinolytic activity returned to pre-treatment levels after 12 weeks of continuous garlic therapy.76
  • Vascular Effects: Vasorelaxant properties of garlic have been noted in multiple pre-clinical studies.77, 78, 79 Cutaneous microperfusion is increased in humans following ingestion of 600mg of garlic80, 81, 82, and vasodilation of conjunctival arterioles and venules occurs at 900mg.83 Garlic may act on the nitric oxide system84, 85, 86 and exert effects on the elastic properties of vasculature87, yielding changes in systemic blood pressure86. It has been suggested that allicin is the component of garlic responsible for nitric oxide-mediated effects.88 Prostaglandins have been identified in garlic extracts which may exert pharmacologic effects89, although this has not been demonstrated in vivo.
  • Chemoprotective/Anti-tumor Effects: Animal studies have reported protective effects of garlic against hepatotoxins6, 90, 7, 8, cyclophosphamide91, adriamycin92 methylcholanthrene93, gentamicin5, 4-nitroquinoline 1-oxide94, and bromobenzene95, 96. Garlic has demonstrated strong inhibition of cancer development in the presence of known tumor promoters including 12-O-tetradecanoylpharbol-13-acetate97, 98 and 7,12-dimethylbenzanthracene99, and phorbol-myristate-acetate100, as well as tumor inducers such as 7,12-dimethylbenzanthracene98 and 1,2-dimethylhydrazine101,102. There is some evidence that the chemical constituents containing allyl groups may be responsible for chemoprotective properties.103 Research has provided evidence of anti-proliferative effects of garlic on human cancer cell lines104, including induction of apoptosis105,106,107,108,109, regulation of cell cycle progression110, and signal transduction modification. Both cellular proliferation111,112 and immune function appear to be affected113,114.
  • Immunologic Effects: The immunologic activity of garlic may include enhanced phagocytosis, lymphocyte proliferation, enhanced killer cell activity and cytokine production, and prevention of immune suppression.115,116,117,118,119,120 There has been suggestion that heating may adversely affect this benefit, related to a loss of alliinase activity121, and that different preparations have variant pharmacologic activities21.
  • Antimicrobial Effects (Bacteria, Fungi, Yeast): Garlic has been demonstrated In vitro to exert activity against multiple pathogens, including bacteria122,123,14,124,125,10,126,127, including resistant strains128, mycobacteria129,130,131, Helicobacter pylori132,133,10, and fungi134,135. Garlic extract has been found to be bactericidal to Histoplasma capsulatum.136 Ajoene alone possesses antibacterial activity against both gram positive and negative bacterial species and inhibits yeast growth In vitro, and the disulfide bond in ajoene may be responsible for these effects.126 The substrate alliin and its enzyme are found in separate but adjacent compartments of the garlic clove, and appear to exert antimicrobial activity when they are joined. Allicin may act via inhibition of thiol-containing and other enzyme systems, DNA, RNA and protein synthesis.124,137,138,20 It has been suggested that garlic oil's antimicrobial activity is more potent than garlic powder on a unit weight basis.139
  • The minimum inhibitory concentration (MIC) of aqueous garlic extract (AGE) against six clinical yeast isolates ranged between 0.8-1.6mg/mL in one study.138 Garlic appeared to alter the structure and integrity of the outer surface of yeast cells as well as decrease their total lipid content. Garlic was also shown to increase phosphatidylserines while decreasing phosphatidylcholines. Oxygen consumption of yeast cells was also reduced by garlic. The anti-candidal activity of AGE was antagonized by thiols including L-cysteine, glutathione and 2-mercaptoethanol. The effect of AGE on the macromolecular synthesis of Candida albicans revealed protein and nucleic acid syntheses to be inhibited, and lipid synthesis to be arrested.140 Antagonism of lipid synthesis may be a component of the anti-candidal activity of garlic.
  • Anti-viral Effects: In vitro studies have demonstrated effects against several viruses141, including influenza B virus, herpes simplex virus type 1141, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, human rhinovirus type 21,2, and cytomegalovirus4. Weber reported that the compound ajoene, found in oil-macerates of garlic, possesses a high level of antiviral activity followed by allicin, allyl methyl thiosulfinate and methyl allyl thiosulfinate.2
  • Glycemic Effects: SACS (S-allyl cysteine sulfoxide), an antioxidant isolated from garlic, has been found to significantly stimulate insulin secretion from beta cells isolated from normal rats.13 However, multiple human studies have failed to demonstrate glycemic effects of garlic.
  • Genitourinary Effects: Chronic garlic ingestion for 70 days has been associated with suppression of spermatogenesis in rats.17

Pharmacodynamics/Kinetics:

  • Garlic compounds are rapidly absorbed through mucous membranes and skin. Excretion is primarily via liver, kidney and intestines.20
  • Nagae142 described the pharmacokinetics of S-Allylcysteine (SAC) in animal models. The authors demonstrated a first pass effect following rapid gastrointestinal absorption; with liver and kidney metabolism.
  • The pharmacokinetics of the vinyldithiins, transformation products of allicin, have been described; maximal concentrations 15-30 minutes after oral absorption.143

References
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